Genomics

Dataset Information

36

Spatial transcriptome analysis reveals Notch pathway-associated prognostic markers in IDH1 wild-type glioblastoma involving the subventricular zone


ABSTRACT: Background: The spatial relationship of glioblastoma (GBM) to the subventricular zone (SVZ) is associated with inferior patient survival. However, the underlying molecular phenotype is largely unknown. We interrogated an SVZ-dependent transcriptome and potential location-specific prognostic markers. Methods: mRNA microarray data of a discovery set (n = 36 GBMs) were analyzed for SVZ-dependent gene expression and process networks using the MetaCoreTM workflow. Differential gene expression was confirmed by qPCR in a validation set of 142 IDH1 wild-type GBMs that was also used for survival analysis. Results: Microarray analysis revealed a transcriptome distinctive of SVZ+ GBM that was enriched for genes associated with Notch signaling. No overlap was found to The Cancer Genome Atlas’s molecular subtypes. Independent validation of SVZ-dependent expression confirmed four genes with simultaneous prognostic impact: overexpression of HES4 (p = 0.034; HR 1.55) and DLL3 (p = 0.017; HR 1.61) predicted inferior, and overexpression of NTRK2 (p = 0.049; HR 0.66) and PIR (p = 0.025; HR 0.62) superior overall survival (OS). Additionally, overexpression of DLL3 was predictive of shorter progression-free survival (PFS) (p = 0.043; HR 1.64). Multivariate analysis revealed overexpression of HES4 to be independently associated with inferior OS (p = 0.033; HR 2.03), and overexpression of DLL3 with inferior PFS (p = 0.046; HR 1.65). Conclusions: We identified four genes with SVZ-dependent expression and prognostic significance, among those HES4 and DLL3 as part of Notch signaling, suggesting further evaluation of location-tailored targeted therapies. Overall design: Comparative transcriptomic analysis of 36 glioblastomas in different locations of the brain.

INSTRUMENT(S): Illumina HumanHT-12 V4.0 expression beadchip

ORGANISM(S): Homo Sapiens

SUBMITTER: Christel Herold-Mende 

PROVIDER: GSE83537 | GEO | 2016-10-26

SECONDARY ACCESSION(S): PRJNA326272

REPOSITORIES: GEO

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Publications

Spatial transcriptome analysis reveals Notch pathway-associated prognostic markers in IDH1 wild-type glioblastoma involving the subventricular zone.

Jungk Christine C   Mock Andreas A   Exner Janina J   Geisenberger Christoph C   Warta Rolf R   Capper David D   Abdollahi Amir A   Friauf Sara S   Lahrmann Bernd B   Grabe Niels N   Beckhove Philipp P   von Deimling Andreas A   Unterberg Andreas A   Herold-Mende Christel C  

BMC medicine 20161026 1


<h4>Background</h4>The spatial relationship of glioblastoma (GBM) to the subventricular zone (SVZ) is associated with inferior patient survival. However, the underlying molecular phenotype is largely unknown. We interrogated an SVZ-dependent transcriptome and potential location-specific prognostic markers.<h4>Methods</h4>mRNA microarray data of a discovery set (n = 36 GBMs) were analyzed for SVZ-dependent gene expression and process networks using the MetaCore™ workflow. Differential gene expres  ...[more]

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